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What are they? What do they do? Martin Rowland

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1 What are they? What do they do? Martin Rowland
Viruses What are they? What do they do? Martin Rowland Philip Allan Publishers © 2015

2 Viruses vary in shape and size
Bacteriophage T4, 225 nm long Adenovirus, 90 nm Rhinovirus, 30 nm Tobacco mosaic virus — rod-shaped, 250 × 18 nm Vaccinia virus — brick-shaped or ovoid, 300 nm × 200 nm × 100 nm Ebola virus, 970 nm Poliovirus, 30 nm Compare with Escherichia coli (a bacterium) 3000 × 1000 nm and a human red blood cell, nm diameter, surface membrane 10 nm thick bacteriophage Ebola adenovirus This slide shows a number of different viruses, with a cell of Escherichia coli and part of a human erythrocyte for comparison. Students often make errors when converting units, e.g. nano- to milli- or vice versa. In addition to focusing on the different viral shapes and scales, teachers could use this slide to reinforce with students the correct conversion of units of length. [1 nm = 10−3 mm; 1 nm = 10−9 m] Philip Allan Publishers © 2015

3 What do viruses have in common?
1 Structure: Extremely small Each consists of a particle (called a virion) outer complex of proteins (the capsid) inner nucleic acid core (DNA or RNA) In addition: some have a lipoprotein envelope outside the capsid some contain enzymes associated with entering host cell and replication of nucleic acid Slide 3 introduces the key structures that students could be expected to recall — virion, capsid and core nucleic acid. Teachers could introduce here the concepts of single-stranded (ss) and double-stranded (ds) nucleic acid, e.g. ssRNA, dsRNA, ssDNA and dsDNA, all of which are found in different viruses. Philip Allan Publishers © 2015

4 A simple example of viral structure
Human papillomavirus (HPV) causes warts in humans The capsid contains two types of protein: L1 (shown in yellow) L2 (shown in red) The double-stranded DNA (shown in blue) is circular Slide 4 shows a simple example of viral structure to help students visualise the capsid and nucleic acid core. The virus shown, the human papillomavirus (HPV), causes warts in humans. Some types of HPV, particularly the sexually transmitted HPV-6 and HPV-18, are carcinogenic (see Biological Sciences Review, April 2010, pages 7 to 9). Philip Allan Publishers © 2015

5 What do viruses have in common?
2 Function: Viruses have no metabolism of their own, e.g. they do not use ATP and are unable to produce proteins Viruses can only be replicated using the metabolism of another living cell (the host) In doing so they cause harm to the host cell Outside a suitable host cell, viruses are inert Slide 5 introduces the basic nature of viruses, i.e. that they lack a metabolism and rely on the metabolism of a host cell to produce new virions. Teachers could use this slide to discuss with students: – whether viruses can be regarded as organisms – the processes that are vital to metabolism (such as the ability to produce/hydrolysis ATP, to replicate nucleic acid or to synthesise proteins) Philip Allan Publishers © 2015

6 Five different viruses
Lambda bacteriophage (λ phage) Tobacco mosaic virus (TMV) Ebola virus Human immunodeficiency virus (HIV) Influenza (‘flu’) virus This slide introduces slides 7 to 11, covering the four viruses named in the Edexcel AS specification B and a fifth named in the second year component of the Edexcel A-level specification B. Teachers following other specifications could delete slides that are not relevant to their students. Philip Allan Publishers © 2015

7 Lambda bacteriophage (λ phage)
Capsid has a head and a tail region Nucleic acid is double-stranded DNA, which is transcribed by the host cell into mRNA Infects the bacterium Escherichia coli Philip Allan Publishers © 2015

8 Tobacco mosaic virus (TMV)
Capsid is a spiral of polypeptides Nucleic acid is single-stranded RNA, which is transcribed by host cell to form mRNA Infects a wide range of plants, especially tobacco and other members of the Solanaceae family Philip Allan Publishers © 2015

9 Ebola virus Capsid of protein
Nucleic acid is single-stranded RNA, which is transcribed by the host cell to form mRNA Infects several types of human cell Philip Allan Publishers © 2015

10 Human immunodeficiency virus (HIV)
Capsid surrounded by phospholipid and glycoprotein envelope Nucleic acid is single-stranded RNA, which is transcribed inside the host to form single-stranded DNA Enzymes include reverse transcriptase Infects macrophages and T helper cells of humans Philip Allan Publishers © 2015

11 Influenza virus Capsid surrounded by phospholipid and glycoprotein envelope Eight short, single-stranded, negative-sense RNA fragments that are transcribed by the host cell to form mRNA Infects epithelial cells of the nose, throat and lungs of mammals Philip Allan Publishers © 2015

12 How does a virus infect a cell?
Proteins on the surface of the virus are complementary to specific proteins (or glycoproteins) on the surface membrane of a target cell For example, HIV attaches to a protein called CD4 found on the surface of T lymphocytes If a random collision is perfectly aligned, the viral protein binds to the protein or glycoprotein on the surface of the target cell The viral nucleic acid then enters the target cell Slide 12 covers the way in which viruses adsorb to their target cells. The concept of ‘complementary’ of proteins or glycoproteins is fundamental in biology, and students will realise it recurs in the induced-fit model of enzyme action, the interaction of antigens with cells of the immune system and, in their second year of study, the transmission of nerve impulses across synapses and the interaction of hormones with their target organs. It is also worth stressing that not all collisions result in adsorption; the collision must be between those parts of molecules that are complementary and at the appropriate speed and angle (models can be used to visualise this concept). In examinations, students often use the term ‘active site’ when referring to complementary proteins; it is useful to stress they should only use this term when referring to an enzyme. Its use elsewhere is incorrect and, consequently, unlikely to be credited in an examination. Philip Allan Publishers © 2015

13 What does the viral nucleic acid do?
Either: Becomes attached to the DNA of the host cell and remains dormant for a period of time This period of time is called latency Infection by Varicella zoster during childhood causes chickenpox. The virus can show latency in nerve cells and, in adulthood, reappear as shingles Herpes virus (cold sores and genital herpes) can also show latency in nerve cells Slide 13 introduces the concept of latency. In addition to the examples given, teachers could remind students of the latency of HIV which, as a concept if not by name, they had learnt about in their GCSE biology course. Philip Allan Publishers © 2015

14 What does the viral nucleic acid do?
or: Takes over control of the host cell causing it to replicate the virus produce new viral capsids assemble new virions release the new virions Slide 14 summarises what happens in the absence of a latency period or when a dormant virus (provirus) is activated. The viral nucleic acid takes control of the host cell’s metabolism, resulting in the production and release of new virions. Teachers could use slides 12, 13 and 14 as an opportunity to discuss with their more able students, e.g. S&C, the likely role of enzymes that many viruses contain and those that, given they are dependent on the activities of the host cell, they might lack. Philip Allan Publishers © 2015

15 The lytic cycle of the λ phage
Slide 15 extends the content of slide 14 in the context of the lytic cycle of the λ phage that infects Escherichia coli. Philip Allan Publishers © 2015

16 ‘Life’ cycle of the flu virus
Viral antigens attach to receptors on lung epithelial cells and trigger endocytosis Viral RNA enters nucleus of epithelial cell where it is transcribed and replicated Copies of viral RNA leave nucleus and are translated by host cell’s ribosomes Viral RNA and proteins assembled by host cell to form new virus particles New virus particles leave host cell, picking up a lipid coat in the process Slide 16 extends the content of slide 14 in the context of the ‘life’ cycle of the influenza virus in humans. Teachers could, again, remind students of the HIV ‘life’ cycle that they learnt for GCSE and use it to compare with the cycles shown in slides 15 and 16. The issues that might usefully be discussed here are: – the nature of the adsorption of the HIV particle by the merging of the phospholipid bilayers of the HIV and the target cell’s surface membrane (compared with the injection of DNA by the λ phage) – the release of new HIV particles by budding from the surface of the infected cell (the virus picking up a coating of phospholipid bilayer in the process) rather than by cell lysis – the role of reverse transcriptase in HIV The lytic cycle of the λ phage could be reintroduced when discussing DNA as the hereditary material (as used in the classic 1952 Hershey-Chase experiments). Philip Allan Publishers © 2015

17 How can viral infections be treated?
Since viruses have no metabolism, they cannot be ‘killed’ Vaccines against one or more viral antigens are effective in reducing the risk of infection Antivirals prevent one or more stages of the viral life cycle. For example: prevent binding of the virus to the target cell inhibit virus-specific enzymes, e.g. those that allow the virus to enter the target cell, allow virus nucleic acid to become incorporated into host DNA, or allow replication of viral nucleic acid Prevention of spread is a key strategy Slide 17 summarises the options for dealing with viral infections. Useful discussion points include: – achieving herd immunity during vaccination programmes – adopting measures that inhibit the host cell’s ability to synthesise new virions without inhibiting those that are essential to its own survival – the reasons why controlling the spread of the virus was so critical in the Ebola outbreaks in West Africa (see main article in this issue of Biological Sciences Review) Philip Allan Publishers © 2015

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